In previous studies in this laboratory, several extracorporeal immunoadsorbents have been developed consisting of immobilized antigens, antibodies and enzymes which have shown a capacity to extract their respective antigens, antibodies and substrates from circulating plasma in vivo. With these systems, disease processes including experimental nephrotoxic glomerulonephritis and hyperacute renal xenograft rejection have been arrested or attenuated. More recently, the application of this approach to systemic lupus erythematosus in man resulted in substantial renal functional and morphologic improvement. We have now extended this approach to therapy of spontaneous breast adenocarcinoma in the dog. Employing formalin stabilized staphyloccocus aureus Cowan I (SAC) embedded in a membrane filtration system we have observed substantial tumoricidal effects in spontaneous canine breast adenocarcinoma. The tumoricidal response is rapid and specific for primary and multiple metastatic sites with minimal toxicity to the host. In some instances, healing of large ulcerated tumor areas has been observed. Serologic and immunohistochemical evaluation of tissue suggests that the tumoricidal response is initiated by tumor specific antibodies which are generated by the extracorporeal perfusion procedure. The proposed studies would extend this approach from dogs to clinical trials in breast adenocarcinoma in humans to include serologic, immunologic and immunohistochemical assessment. Concomitantly, studies will continue in the canine model employing extracorporeal perfusion over purified protein A, aggregated IgG columns and forced flow electrophoresis. Promising results have shown tumoricidal effects associated with these systems which may be markedly augmented by the concomitant use of carefully timed cytotoxic drug therapy in the post-perfusion period. Projected studies will continue the assessment of these systems and their interaction with existing modes of chemotherapy and immunotherapy. Improvements in extracorporeal cell-separation technology and refinement in immobilization techniques will be tested in vivo in our canine models of SLE and breast cancer. Extracorporeal immunoadsorption may thus represent a major new therapeutic instrument for clinicians which at the same time may enhance our understanding of the pathophysiology of numerous neoplastic and autoimmune diseases.